The product of the obese gene (ob) is the protein leptin, which is synthesized in and secreted from adipocytes. Fasting serum leptin concentrations are closely related to body fat content and are higher in obese than in normal-weight individuals. Glycerol release from fat cells can be studied by stable isotope dilution mass spectrometry and is a marker of lipolysis. Leptin may contribute to body weight regulation. Overproduction of leptin in certain pathologic conditions such as acquired immunodeficiency syndrome (AIDS) might in principle contribute to the low body fat content associated with body wasting. We measured fasting serum leptin levels by radio-immunoassay in individuals infected with the human immunodeficiency virus (HIV) and in a group of healthy lean men to determine whether HIV infection increases leptin levels. Energy intake in the HIV-infected men, assessed from 3-day intake records, was within the normal range. These findings extend the hypothesis that circulating leptin concentrations directly reflect adipose tissue mass, even in HIV-infected men with low body fat content. These findings do not support the hypothesis that HIV infection is associated with high circulating leptin concentrations and suggest that low leptin levels do not stimulate food intake in HIV-infected individuals.